The role of microglia in hyperalgesia priming and electroacupuncture intervention for pain transition

To explore the mechanism of hyperalgesia priming (HP) and evaluate the intervention effect of electroacupuncture (EA) on pain transition.

Fifty-nine male C57 mice were used for 4 separate experiments. In the first experiment, the mice were divided into a control group, a sham sensitization group, and a sensitization group, with 5 mice per group. In the second experiment, the mice were divided into a sham sensitization group, a sensitization group, and a sensitization + EA group, with 5 mice per group. The third experiment consisted of a sensitization group and a sensitization + minocycline group, with 7 mice per group. In the fourth experiment, the mice were divided into a sensitization group, a sensitization + EA + PBS group, and a sensitization + EA + colony-stimulating factor (CSF) group, with 5 mice per group. A HP mouse model was established via consecutive intraplantar injections of carrageenan and prostaglandin E2. EA was applied to bilateral “Zusanli” (ST36) and “Kunlun” (BL60) for 30 min, once daily for 8 d. Mechanical paw withdrawal thresholds (PWTs) were measured at different time points to assess pain transition and the effect of EA. Immunofluorescence was used to detect the activation of microglia marker (Iba1) and astrocyte marker (GFAP) in the spinal cord dorsal horn. Intrathecal injection of minocycline was also administered, and its impacts on Iba1 activation and PWTs were tested. After the experiment, skeleton and Sholl analyses were performed to analyze the morphology of microglia. To further examine the role of CSF-1, the factor was administered intrathecally to assess its influence on the effects of EA.

In the pain transition mouse model, the PWTs at various time points decreased significantly (P<0.01). After modeling, the microglia was activated (P<0.01), but the astrocyte was not. EA increased the PWTs in pain transition mice (P<0.01) and suppressed microglia activation (P<0.01). Intrathecal minocycline administration inhibited microglia activation, reduced Iba1 expression in the spinal cord dorsal horn (P<0.01), and effectively reversed the PWTs reduction (P<0.01). Subsequent intrathecal CSF-1 injection promoted microglia activation and blocked the analgesic effect of EA in the model mice (P<0.01).

Microglia activation is critical in pain transition. EA can alleviate hyperalgesia in HP mice by inhibiting microglia activation.